Abstract: The present invention relates to regulation of cardiac contractile function. The present invention is based on the discovery that microRNAs contribute to the loss of cardiac contractility. Specifically, miR-25 binds to SERCA2a which results in a loss of function and interferes with Ca2+ handling. Accordingly, the present invention relates to methods of increasing cardiac contractile function by inhibiting miR-25. The invention further provides methods to identify agents that can modulate miR-25 activity, including high throughput screening methods, and provides a means to identify agents that are useful for treating patients having cardiac contractile function associated disorders.

Abstract: Methods and small molecule compounds for inhibition of cancer cell proliferation are provided. One example of a class of compounds that may be used is represented by the compound of Formula I or a pharmaceutically acceptable salt, N-oxide or solvate thereof, wherein A, B, D, E, F, G, I, J, R, R1, R2, R2?, R3, R4, R5, R6, R7, R8, R9 are as described herein.

Abstract: Methods and small molecule compounds for stem cell differentiation and treatment of animals with diseases are provided. One example of a class of compounds that may be used is represented by the compound of Formula I and II: or a pharmaceutically acceptable salt or solvate thereof, wherein A, X, Q, R1, R2, R3, R4 are as described herein.

Abstract: Small molecule compounds and methods for stem cell differentiation are provided herein. An example of a class of compounds that may be used to practice the methods disclosed herein is represented by enantiomerically pure isomers of compounds of Formula I: or a chirally pure stereoisomer, pharmaceutically acceptable salt, or solvate thereof, wherein R1, R2, R3, R4, R5, R5?, R6, R6?, R7, R7? are as described herein.

Abstract: The present invention provides screening methods for the detection of agents that affect various aspects of ?-cell biology, particularly insulin gene expression. Screening methods are also provided for detection of agents that affect ?-cell differentiation from progenitor cells. Additionally, agents identified using such methods are provided and are useful for increasing insulin gene expression and reducing lipotoxicity.

Abstract: The present invention provides a method, system and composition for screening drug candidates for cardiotoxicity and for novel drugs that effect cardiomyocyte contractility and function. The invention provides an efficient and reliable screening assay to detect the effect of new and potential drug candidates on cardiomyocyte calcium flux, membrane depolarization, and/or the propagation of action potentials.

Abstract: Methods and small molecule compounds for stem cell differentiation are provided. One example of a class of compounds that may be used is represented by the compound of Formula I: or a pharmaceutically acceptable salt or solvate thereof, wherein R1, R2, R3, R4, R5, R5?, R6, R6?, R7, R7? are as described herein.

Abstract: The finding that Dickkopf1 (Dkk1) is a dual function protein demonstrates a mechanism for the coordination of cell migration and antagonism of Wnt/?-catenin signaling during developmental and pathological processes. The profile of Dkk proteins expressed by human breast cancers correlates with indicators of outcome: Dkk1 associates with markers of poor prognosis whereas expression of single function Dkk2 or Dkk3 (which inhibit Wnt/?-catenin signaling and promote migration, respectively) correlates with phenotypes reflective of good prognosis. Therefore, the pro-migratory activities of Dkk1 and 3 identified here offer new insights into breast cancer progression and a potential avenue for therapeutic intervention.

Abstract: Compositions and methods are provided for screening for compounds that modulate insulin promoter activity. Vectors that express green fluorescent protein under the control of the human insulin promoter are introduced into mouse and human cells in which the insulin promoter is expressed in a glucose-responsive manner. Such cells are then used to screen for compounds that modulate insulin promoter activity.

Abstract: The finding that Dickkopf1 (Dkk1) is a dual function protein demonstrates a mechanism for the coordination of cell migration and antagonism of Wnt/?-catenin signaling during developmental and pathological processes. The profile of Dkk proteins expressed by human breast cancers correlates with indicators of outcome: Dkk1 associates with markers of poor prognosis whereas expression of single function Dkk2 or Dkk3 (which inhibit Wnt/?-catenin signaling and promote migration, respectively) correlates with phenotypes reflective of good prognosis. Therefore, the pro-migratory activities of Dkk1 and 3 identified here offer new insights into breast cancer progression and a potential avenue for therapeutic intervention.

Abstract: The finding that Dickkopf1 (Dkk1) is a dual function protein demonstrates a mechanism for the coordination of cell migration and antagonism of Wnt/?-catenin signaling during developmental and pathological processes. The profile of Dkk proteins expressed by human breast cancers correlates with indicators of outcome: Dkk1 associates with markers of poor prognosis whereas expression of single function Dkk2 or Dkk3 (which inhibit Wnt/?-catenin signaling and promote migration, respectively) correlates with phenotypes reflective of good prognosis. Therefore, the pro-migratory activities of Dkk1 and 3 identified here offer new insights into breast cancer progression and a potential avenue for therapeutic intervention.

Abstract: Disclosed are methods and compositions relating to antagonists of HNF4?.

Abstract: Methods and small molecule compounds for stem cell differentiation are provided.

Abstract: Compositions and methods are provided for screening for compounds that modulate insulin promoter activity. Vectors that express green fluorescent protein under the control of the human insulin promoter are introduced into mouse and human cells in which the insulin promoter is expressed in a glucose-responsive manner. Such cells are then used to screen for compounds that modulate insulin promoter activity.

Abstract: The finding that Dickkopf1 (Dkk1) is a dual function protein demonstrates a mechanism for the coordination of cell migration and antagonism of Wnt/?-catenin signaling during developmental and pathological processes. The profile of Dkk proteins expressed by human breast cancers correlates with indicators of outcome: Dkk1 associates with markers of poor prognosis whereas expression of single function Dkk2 or Dkk3 (which inhibit Wnt/?-catenin signaling and promote migration, respectively) correlates with phenotypes reflective of good prognosis. Therefore, the pro-migratory activities of Dkk1 and 3 identified here offer new insights into breast cancer progression and a potential avenue for therapeutic intervention.

Abstract: The present invention provides screening methods for the detection of agents that affect various aspects of ?-cell biology, particularly insulin gene expression. Screening methods are also provided for detection of agents that affect ?-cell differentiation from progenitor cells. Additionally, agents identified using such methods are provided and are useful for increasing insulin gene expression and reducing lipotoxicity.

Abstract: The finding that Dickkopf1 (Dkk1) is a dual function protein demonstrates a mechanism for the coordination of cell migration and antagonism of Wnt/?-catenin signaling during developmental and pathological processes. The profile of Dkk proteins expressed by human breast cancers correlates with indicators of outcome: Dkk1 associates with markers of poor prognosis whereas expression of single function Dkk2 or Dkk3 (which inhibit Wnt/?-catenin signaling and promote migration, respectively) correlates with phenotypes reflective of good prognosis. Therefore, the pro-migratory activities of Dkk1 and 3 identified here offer new insights into breast cancer progression and a potential avenue for therapeutic intervention.

Abstract: The present invention relates to compositions and methods for stimulating differentiation of stem cells into cardiac cells. The methods of the invention involve contacting a population cells comprising stem cells with at least one Wnt antagonist, such as a polypeptide or polypeptide fragment. In certain embodiments, the methods of the invention involve Dkk proteins or fragments, homologs, derivatives, variants, or peptidomimetics thereof.